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MYH9 has been proposed as a major genetic risk locus for a spectrum ofnon-diabetic end stage kidney disease (ESKD). We use recently releasedsequences from the 1000 Genomes Project to identify two western Africanspecific missense mutations (S342G and I384M) in the neighbouring APOL1 gene,and demonstrate that these are more strongly associated with ESKD thanpreviously reported MYH9 variants. We also show that the distribution of theserisk variants in African populations is consistent with the pattern of Africanancestry ESKD risk previously attributed to the MYH9 gene. Additionalassociations were also found among other members of the APOL gene family, andwe propose that ESKD risk is caused by western African variants in members ofthe APOL gene family, which evolved to confer protection against pathogens,such as Trypanosoma.

human genetics

Preliminary Report: Missense mutations in the APOL gene family are  associated with end stage kidney disease risk previously attributed to the  MYH9 gene